A Polynesian-specific CETP missense variant lowers CETP activity by 27.9% and improves the lipid profile (HGG Adv 2023)

Original title: A Polynesian-specific missense CETP variant alters the lipid profile

HGG Adv · 8 May 2023 · 7

Moors J, Krishnan M, Sumpter N, Takei R, Bixley M, Cadzow M, Major TJ, Phipps-Green A, Topless R, Merriman M, Rutledge M, Morgan B et al.

While common pan-population CETP polymorphisms are known to associate with serum lipid profiles and cardiovascular disease, researchers sequenced CETP in Maori and Pacific people and identified a population-specific missense variant, rs1597000001 (p.Pro177Leu), associated with higher HDL cholesterol and lower LDL cholesterol. Each copy of the minor allele was associated with HDL cholesterol higher by 0.236 mmol/L and LDL cholesterol lower by 0.133 mmol/L, an effect on HDL-C comparable to known CETP Mendelian loss-of-function mutations that cause CETP deficiency, consistent with functional data showing rs1597000001 lowers CETP activity by 27.9%. The study highlights the value of population-specific genetic analyses, previously underrepresented in genomic research, for identifying novel CETP variants relevant to lipid metabolism and cardiovascular health equity.

Original abstract

Identifying population-specific genetic variants associated with disease and disease-predisposing traits is important to provide insights into the genetic determinants of health and disease between populations, as well as furthering genomic justice. Various common pan-population polymorphisms at CETP associate with serum lipid profiles and cardiovascular disease. Here, sequencing of CETP identified a missense variant rs1597000001 (p.Pro177Leu) specific to Māori and Pacific people that associates with higher HDL-C and lower LDL-C levels. Each copy of the minor allele associated with higher HDL-C by 0.236 mmol/L and lower LDL-C by 0.133 mmol/L. The rs1597000001 effect on HDL-C is comparable with CETP Mendelian loss-of-function mutations that result in CETP deficiency, consistent with our data, which shows that rs1597000001 lowers CETP activity by 27.9%. This study highlights the potential of population-specific genetic analyses for improving equity in genomics and health outcomes for population groups underrepresented in genomic studies.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.